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Updated: Feb 17, 2026

Multiplexed Fluorescent Immunohistochemical Staining of Four Endometrial Immune Cell Types in Recurrent Miscarriage
Published on: August 4, 2021
Decidual CD68+ HLA-DR+ CD163- M1 macrophages increase in miscarriages with normal fetal chromosome
Shigeki Shimada1, Yasuhiko Ebina2, Norifumi Iijima3
1Mommy's Clinic Chitose, Chitose, Japan.
Problem:
Is an abnormal increase or decrease of M1/M2 macrophages observed in the deciduae of miscarriages with normal fetal chromosome (MN)?
Methods Of Study:
Deciduae of 18 MN and 26 miscarriages with abnormal fetal chromosome (MA) were obtained. Additionally, deciduae from 15 women whose pregnancies ended in induced abortions (IA) and endometriums at the mid-luteal phase from 19 non-pregnant women endomeriums of mid-luteal phases (EM) were obtained. Macrophages were analyzed by flow cytometry using monoclonal antibodies for CD68, HLA-DR, and CD163.
Results:
M1 macrophages, defined as CD68+ HLA-DR+ CD163- cells, increased in MN compared with MA or IA. M2 macrophages, defined as CD68+ HLA-DR- CD163+ cells, increased in the deciduae of MA and IA compared with EM. However, this increase was not observed in the deciduae of MN.
Conclusion:
Our findings of phenotypic characters of decidual macrophages in MN provide additional evidence that M2 polarization is favorable for the maintenance of early stages of pregnancy.
Insights
In miscarriages with normal chromosomes, M1 macrophages increase while M2 macrophages do not, suggesting M2 polarization is crucial for maintaining early pregnancy.
Area of Science:
- Reproductive immunology
- Maternal-fetal interface immunology
Background:
- Decidual macrophages play a critical role in pregnancy maintenance.
- Understanding macrophage polarization (M1/M2) in miscarriage is essential for identifying causes and potential interventions.
Purpose of the Study:
- To investigate the M1/M2 macrophage phenotypes in the decidua of miscarriages with normal fetal chromosomes (MN).
- To compare these phenotypes with miscarriages of abnormal fetal chromosomes (MA), induced abortions (IA), and non-pregnant endometrium (EM).
Main Methods:
- Decidual tissues from MN, MA, IA, and EM groups were analyzed.
- Flow cytometry was employed using monoclonal antibodies (CD68, HLA-DR, CD163) to identify and quantify macrophage subsets.
Main Results:
- M1 macrophages (CD68+ HLA-DR+ CD163-) were elevated in MN compared to MA or IA.
- M2 macrophages (CD68+ HLA-DR- CD163+) increased in MA and IA compared to EM, but not in MN.
Conclusions:
- The altered M1/M2 macrophage balance in MN suggests a potential role in pregnancy loss.
- Findings support the hypothesis that M2 macrophage polarization is favorable for early pregnancy maintenance.

